Estrogen-related receptor gamma

ESRRG
Identifiers
Aliases	ESRRG, ERR3, ERRgamma, NR3B3, estrogen related receptor gamma, ERRg, ERR-gamma
External IDs	OMIM: 602969; MGI: 1347056; GeneCards: ESRRG
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1KV6, 1TFC, 1VJB, 2E2R, 2EWP, 2GP7, 2GPO, 2GPP, 2GPU, 2GPV, 2P7A, 2P7G, 2P7Z, 2ZAS, 2ZBS, 2ZKC
Gene location (Human) Chr. Chromosome 1 (human) Band 1q41 Start 216,503,246 bp End 217,137,755 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1|1 H5- H6 Start 187,340,988 bp End 187,947,082 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pons kidney tubule endothelial cell renal medulla Brodmann area 23 right ventricle parotid gland thoracic diaphragm Epithelium of choroid plexus biceps brachii Top expressed in pontine nuclei deep cerebellar nuclei medial vestibular nucleus epithelium of stomach lateral geniculate nucleus submandibular gland pineal gland globus pallidus dorsal tegmental nucleus facial motor nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific zinc ion binding AF-2 domain binding metal ion binding steroid hormone receptor activity steroid binding protein binding DNA-binding transcription factor activity, RNA polymerase II-specific nuclear receptor activity Cellular component nucleoplasm nucleus Biological process regulation of transcription, DNA-templated transcription, DNA-templated positive regulation of transcription, DNA-templated retinoic acid receptor signaling pathway transcription initiation from RNA polymerase II promoter positive regulation of transcription by RNA polymerase II steroid hormone mediated signaling pathway positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 2104 26381 Ensembl ENSG00000196482 ENSMUSG00000026610 UniProt P62508 P62509 RefSeq (mRNA) NM_001134285 NM_001243505 NM_001243506 NM_001243507 NM_001243509 NM_001243510 NM_001243511 NM_001243512 NM_001243513 NM_001243514 NM_001243515 NM_001243518 NM_001243519 NM_001438 NM_206594 NM_206595 NM_001350122 NM_001350123 NM_001350124 NM_001350125 NM_001243792 NM_011935 NM_001357534 NM_001357535 NM_001357536 RefSeq (protein) NP_001127757 NP_001230434 NP_001230435 NP_001230436 NP_001230438 NP_001230439 NP_001230440 NP_001230441 NP_001230442 NP_001230443 NP_001230444 NP_001230447 NP_001230448 NP_001429 NP_996317 NP_996318 NP_001337051 NP_001337052 NP_001337053 NP_001337054 NP_001230721 NP_036065 NP_001344463 NP_001344464 NP_001344465 Location (UCSC) Chr 1: 216.5 – 217.14 Mb Chr 1: 187.34 – 187.95 Mb PubMed search
Wikidata
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Estrogen-related receptor gamma (ERR-gamma), also known as NR3B3 (nuclear receptor subfamily 3, group B, member 3), is a nuclear receptor that in humans is encoded by the ESRRG (EStrogen Related Receptor Gamma) gene. It behaves as a constitutive activator of transcription, and induces the expression of the transcription regulator PERM1 in skeletal muscles.

This protein is a member of nuclear hormone receptor family of steroid hormone receptors. No physiological activating ligand is known for this orphan receptor, but 4-hydroxytamoxifen and diethylstilbestrol act as inverse agonists and deactivate ESRRG. It also seems to be the target of bisphenol A (see below).

Bisphenol A binding

There is evidence that bisphenol A functions as a xenoestrogen by binding strongly to ERR-γ. BPA as well as its nitrated and chlorinated metabolites seems to binds strongly to ERR-γ (dissociation constant = 5.5 nM), but not to the estrogen receptor (ER)., BPA binding to ERR-γ preserves its basal constitutive activity. It can also protect it from deactivation from the selective estrogen receptor modulator 4-hydroxytamoxifen.

Different expression of ERR-γ in different parts of the body may account for variations in bisphenol A effects. For instance, ERR-γ has been found in high concentration in the placenta, explaining reports of high bisphenol A accumulation there.

Medical significance

Pathogenic mutations in ESRRG have been associated with movement dysfunction as part of a disorder called congenital nonprogressive movement disorder with ataxia and eye movement abnormalities (CONMAE). Those affected by this autosomal dominant disorder display atypical eye movements (especially strabismus), low muscle tone (hypotonia), and an unsteady gait (ataxia). Many also have difficulty articulating, but otherwise don't show cognitive impairment.

References

Further reading